Jacob M. Rowe, MD, of Rambam Medical Center, Haifa, Israel,
reported the intent-to-treat analysis at the 43rd Annual Meeting of the
American Society of Hematology (abstract 2009) on behalf of researchers in an
ongoing joint Medical Research Council/Eastern Cooperative Oncology Group study
(E2993).

All patients in this protocol receive two phases of standard
induction chemotherapy. If the regimen produces a complete response, patients
are assigned to allogeneic BMT if they have an HLA-matched sibling donor and
are age 50 or under. Other complete remission patients are randomized to either
standard consolidation/maintenance therapy for 2½ years or autologous BMT.

All patients receive identical intensification with high-dose
methotrexate prior to undergoing their assigned or randomized therapy.

Over 1,200 patients have been registered, 93% of whom achieved
a complete remission. The median age is 30 years (range, 14 to 60 years). The
induction death rate is 5%.

Dr. Rowe’s presentation was based on 173 Ph-negative patients
assigned to allogeneic BMT and 264 Ph-negative patients who were randomized.
Standard risk was defined as Ph-negative, age over 35 years, time to complete
remission longer than 4 weeks, and white blood cell count below 30,000/µL for
B lineage disease and below 100,000/µL for T lineage disease.

Overall survival was 44% at 5 years and 35% at 7 years in the
Ph-negative patients. "We have over 100 patients already out past 5
years," Dr. Rowe said.

The 5-year event-free survival was 54% in the Ph-negative
patients who had allogeneic BMT vs 34% for all randomized Ph-negative patients
(P = .04). The 5-year overall survival was 54% vs 43%, respectively (P = .4),
and the 5-year relapse rate was 23% vs 61% (P = .001), illustrating what Dr.
Rowe described as "a very potent graft-vs-leukemia effect for leukemia
patients in first remission."

Analysis by Risk Group

The most impressive differences were for standard-risk patients
(see Table). In this group, event-free survival was 67% with allogeneic BMT vs
44% for the randomized patients; overall survival was 69% vs 50%, respectively;
and the relapse rate was 15% vs 51%, respectively.

"For each risk subgroup, the allogeneic group appears to
do better than the randomized cohort, but these are small numbers," Dr.
Rowe said. In the best subgroup, overall survival was 80% for allogeneic BMT
for B lineage, standard-risk patients vs 58% for similar patients in the
randomized population.

"Even though we are dealing with relatively small numbers,
this is notable because there has been a persistent objection to submitting
standard-risk patients, particular T-lineage patients, to transplant, because
they do well with standard therapy," he said. "We agree that they do
well, with a 60% overall survival in the literature, but they appear to do even
better with allogeneic transplant."

He concluded that allogeneic BMT "can provide a potent
antileukemia effect to all adult patients with ALL in first complete remission.
Despite increased early toxicity and a transplant-related mortality of 21%,
allogeneic BMT provides favorable long-term results."

Overall Survival an Issue

The lack of significant difference in overall survival
associated with allogeneic BMT for the patients as a whole sparked considerable
discussion. One attendee said that since overall survival was not changed for
the group as a whole, "why should I recommend this very toxic procedure to
a patient?"

Dr. Rowe said that the reason was the greater chance of a cure
at 5 years. He attributed the lack of significance in overall survival to study
statisticians’ use of log-rank tests, which he said "may not be the most
appropriate, as this is an ongoing study."